CN100548979C - A kind of method of synthetic 3-methyl amino indole compound - Google Patents
A kind of method of synthetic 3-methyl amino indole compound Download PDFInfo
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- CN100548979C CN100548979C CNB2007100364084A CN200710036408A CN100548979C CN 100548979 C CN100548979 C CN 100548979C CN B2007100364084 A CNB2007100364084 A CN B2007100364084A CN 200710036408 A CN200710036408 A CN 200710036408A CN 100548979 C CN100548979 C CN 100548979C
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Abstract
The invention provides a kind of effectively by chirality phosphoric acid as catalyzer, by the method for the synthetic 3-methyl amino indole compound of sulfimide and the high enantioselectivity of benzazolyl compounds high-level efficiency.Compare with existing method, this method is applicable to the Benzazole compounds and the sulfonyl imide compounds of number of different types, and the reaction conditions gentleness is easy and simple to handle.In addition, need not in the reaction to add any metal salt compound, thereby help medicine production and processing.And the productive rate of reaction is also better, the enantioselectivity height.
Description
Technical field
The present invention relates to a kind of method of synthetic 3-methyl amino indole compound, relate in particular to a kind of method of 3-methyl amino indole compound of synthesis of optically active.This method is the Friedel-Crafts reaction by acid catalyzed sulfimide of chiral phosphorus and benzazolyl compounds, and this reaction can realize that the high enantioselectivity of high-level efficiency ground synthesizes the 3-methyl amino indole compound.
Background technology
In recent years, organic molecule catalysis has caused extensive concern [(a) Seayad, the J. of academia and industry member in worldwide owing to advantages such as it are easily synthetic, and structural modification is convenient, and heavy metal free is residual; List, B.Org.Biomol.Chem.2005,3,719-724. (b) Dalko, P.I.; Moisan, L.Angew.Chem.Int.Ed.2004,43,5138-5175.], wherein the asymmetry catalysis of being realized as catalyzer by chirality phosphoric acid is being obtained development [(a) Akiyama, T. rapidly especially over nearly 3 years; Itoh, J.; Yokota, K.; Fuchibe, K.Angew.Chem.Int.Ed.2004,43,1566-1568. (b) Uraguchi, D.; Terada, M.J.Am.Chem.Soc.2004,126,5356-5357. (c) Uraguchi, D.; Sorimachi, K.; Terada, M.J.Am.Chem.Soc.2004,126,11804-11805.], in this field, we have developed the Friedel-Crafts reaction by acid catalyzed sulfimide of chiral phosphorus and benzazolyl compounds, the synthetic 3-methyl amino indole compound that this reaction can the high enantioselectivity of high-level efficiency, and this compounds is present in natural and non-natural indole alkaloid and indole derivatives [(a) Jia, the Y.-X. of a large amount of biologically actives; Xie, J.-H.; Duan, H.-E.; Wang, L.-X.; Zhou, Q.-L.Org.Lett.2006,8,1621-1624. (b) Johannsen, M.Chem.Commun.1999,2233-2234. (c) Somei, M.; Yamada, F.Nat.Prod.Rep.2004,21,278-311. (d) Faulkner, D.J.Nat.Prod.Rep.2002,19,1-48. (e) Bosch, J.; Bennasar, M.-L.Synlett 1995,587-596.].The asymmetric reduction reaction report to sulfimide and indoles is less in the document at present, reaction needs several days reaction times mostly, wherein all there is metal to participate in reaction mostly, thereby find a kind of easy to operately, and the method for the synthetic 3-methyl amino indole compound of the high enantioselectivity of high-level efficiency is the emphasis and the difficult point of this respect.Inventor development utilize this organic micromolecule catalyst of chirality phosphoric acid, this reaction of catalysis in several minutes to a few hours has great significance to synthetic this type of compound.
Summary of the invention
The problem that will solve of the present invention provides a kind of method of effectively synthetic 3-methyl amino indole compound, and the method for the 3-methyl amino indole compound of the high enantioselectivity of a kind of high-level efficiency ground synthesis of optically active especially is provided.
Method of the present invention is a kind of method of effectively synthesizing the 3-methyl amino indole compound by sulfimide and benzazolyl compounds.This method is as catalyzer by organic phosphoric acid.Especially can be during as catalyzer with the chirality organic phosphoric acid by the 3-methyl amino indole compound of the synthesis of optically active of sulfimide and the high enantioselectivity of benzazolyl compounds high-level efficiency.
The method synthetic 3-of institute methyl amino indole compound general molecular formula of the present invention is:
When using the chirality organic phosphoric acid as catalyzer, institute's synthetic 3-methyl amino indole compound is optically active, and its general formula is
Wherein
*Represent chiral carbon atom.
In the formula: R
1Be selected from H, Ac, Boc, Bz, Fmoc, Troc, C arbitrarily
1-C
16Alkyl, wherein on behalf of ethanoyl, Boc, Ac represent tertbutyloxycarbonyl, Bz to represent benzoyl, Fmoc to represent fluorenylmethyloxycarbonyl, Troc to represent 2,2, the 2-trichloro-ethoxycarbonyl; R
2, R
4, R
5, R
6Or R
7Be selected from H, halogen, C arbitrarily
1-C
16-oxyl, C
1-C
16Alkyl or amino; R
8Be selected from H, ester group, phosphate-based, C arbitrarily
1-C
16Alkyl; R
9Be selected from the C that comprises cyclohexyl arbitrarily
1-C
16Alkyl, heteroaryl, replacement aryl as:
R wherein
11, R
12, R
13, R
14, R
15Be selected from H, halogen, C arbitrarily
1-C
16Perfluoroalkyl, nitro, C
1-C
16-oxyl, C
1-C
16Alkyl, amino, also can be the conjugation aryl; R
10Be selected from aryl, the C of replacement arbitrarily
1-C
16Alkyl, the substituting group on the described substituted aryl is recommended as H, halogen, C
1-C
16-oxyl, C
1-C
16Alkyl or amino.Above-mentioned halogen can be F, Cl, Br or I.Above-mentioned alkyl can be alkyl, thiazolinyl, alkynyl, cycloalkyl or benzyl.
3-methyl amino indole compound of the present invention is to be raw material with sulfimide and benzazolyl compounds, in the presence of organic solvent, is that catalyst reaction makes with organic phosphoric acid especially chirality organic phosphoric acid, can be represented by the formula:
The structural formula of benzazolyl compounds is:
R wherein
1, R
2, R
4, R
5, R
6, R
7As previously mentioned; R
3Be H; The structural formula of sulfimide is:
R
8, R
9, R
10As previously mentioned.The general structure of catalyzer is (be any optically pure structure or its enantiomorph or raceme, not limit by diagram):
R wherein
16, R
17, R
18, R
19, R
20Be selected from H, C arbitrarily
1-C
16Silica-based, aryl, conjugation aryl such as the naphthyl, anthryl, the phenanthryl that replace of alkyl, replacement.Substituting group on silica-based, the aryl that replaces of described replacement is recommended as H, halogen, CF
3, nitro, C
1-C
16-oxyl, C
1-C
16Alkyl or amino.
The mol ratio of described sulfimide, benzazolyl compounds, chirality organic phosphoric acid is recommended as 1: 1-10: 0.0001-1, further 1: 1-10: 0.01-1, especially the mol ratio of recommendation response is: sulfimide: benzazolyl compounds: the chirality organic phosphoric acid is 1: 1-4: 0.05-0.2.Temperature of reaction is recommended as-78 ℃ to 100 ℃, and further the recommendation response temperature is :-60 ℃ to 25 ℃.Reaction times was recommended as 10 minutes-48 hours.R wherein
1, R
2, R
3, R
4, R
5, R
6, R
7, R
8, R
9, R
10, R
11, R
12, R
13, R
14Ditto described.
The alkyl of being mentioned among the present invention, thiazolinyl, alkynyl,-oxyl, ester group, phosphate-based, acyl group etc., unless otherwise indicated, all recommending carbon number is 1～18 group, and further to recommend carbon number be 1～10, and especially recommending carbon number is 1～4.The cycloalkyl of being mentioned among the present invention unless otherwise indicated, refers to that all carbon number is 3～18 group, further recommending carbon number is 3～10, and especially recommending carbon number is 3～7.The aryl of being mentioned among the present invention unless otherwise indicated, all refers to phenyl, naphthyl, C
5～C
10Contain N, O, the heterocyclic radical of S is recommended as phenyl.The heteroaryl of mentioning among the present invention is recommended C
5～C
10Contain N, O, the heterocyclic radical of S.
In the inventive method, described organic solvent can be polarity or non-polar solvent.As benzene, tetracol phenixin, sherwood oil, tetrahydrofuran (THF), dimethyl formamide, ether, methylene dichloride, trichloromethane, toluene, dimethylbenzene, hexanaphthene, normal hexane, normal heptane, dioxane, acetonitrile etc.
Adopt the inventive method products therefrom can pass through recrystallization, thin-layer chromatography, methods such as column chromatography underpressure distillation are separated.As the method with recrystallization, recommending solvent is the mixed solvent of polar solvent and non-polar solvent.Recommend solvent to can be methylene dichloride---normal hexane, Virahol---sherwood oil, ethyl acetate---sherwood oil, ethyl acetate---normal hexane, Virahol---ethyl acetate---mixed solvents such as sherwood oil.With thin-layer chromatography and column chromatography method, used developping agent is the mixed solvent of polar solvent and non-polar solvent.Recommend solvent to can be Virahol---sherwood oil, ethyl acetate---sherwood oil, ethyl acetate---normal hexane, Virahol---ethyl acetate---mixed solvents such as sherwood oil, its volume ratio can be respectively: polar solvent: non-polar solvent=1: 0.1-500.For example: ethyl acetate: sherwood oil=1: 0.1-50, Virahol: sherwood oil=1: 0.1-500.
The invention provides some new 3-methyl amino indole compounds
R for example wherein
1Be H; R
5Be H, Br, methyl or methoxy, R
6Be H or Cl; R
2, R
4, R
7Be H; R
8Be H; R
9Be phenyl, o-methoxyphenyl or p-methylphenyl; R
10Be phenyl or p-methylphenyl; And work as R
5Be methyl or R
6Be Cl, or R
9During for o-methoxyphenyl, R
10Be phenyl.This compounds can remove alkylsulfonyl through the reaction of routine and go up amino protecting group such as carbobenzoxy-(Cbz), uses thereby have widely.
The invention provides a kind of effectively by phosphoric acid especially chirality phosphoric acid as catalyzer, by the method for the synthetic 3-methyl amino indole compound of sulfimide and the high enantioselectivity of benzazolyl compounds high-level efficiency.Compare with existing method, this method is applicable to the Benzazole compounds and the sulfonyl imide compounds of number of different types, and the reaction conditions gentleness is easy and simple to handle.In addition, need not in the reaction to add any metal salt compound, thereby help medicine production and processing.And the productive rate of reaction is also better, is generally 60%-98%, and the enantioselectivity height is generally 58%-＞99%.
Embodiment
To help to understand the present invention by following embodiment, but not limit content of the present invention.
Embodiment 1: the preparation of chirality phosphoric acid
Under the room temperature argon shield; in an exsiccant reaction tubes, diphenol or dihydroxyl derivative (0.5mmol) are dissolved in the 1mL exsiccant pyridine; under quick stirring condition, the phosphorus oxychloride of (1.0mmol) is added drop-wise in the system stirring at room 3 hours slowly.1mL water is added drop-wise in the system slowly, again stirring at room 30 minutes.Add the methylene dichloride dissolving, with 1N aqueous hydrochloric acid (10mL * 3) washing, organic layer anhydrous sodium sulfate drying, decompression is revolved and is desolvated, and the residue column chromatography for separation gets product.
C1:(S)-3,3 '-[3,5-two (trifluoromethyl) phenyl] 2-1,1 '-binaphthol phosphoric acid
(S)-3，3′-[3，5-Bis(trifluoromethyl)phenyl]2-1，1′-binaphthyl?phosphate
Solid, 89% productive rate.IR(CHCl
3)1620，1501，1474，1379，1325，1281，1246，1178，1140，1109，1084，1024，988，964，891，870，867cm
-1.
1H?NMR(400MHz，CDCl3)δ＝8.01(s，8H)，7.61-7.58(m，4H)，7.42-7.39(m，4H).
31P?NMR(189MHz，CDCl
3)δ＝4.61.
13C?NMR(100MHz，CDCl
3)δ＝143.5(d，J
P-C＝9.3Hz)，138.6，132.3，132.0，131.4，131.4(q，JC-F＝33.4Hz)，131.1(d，J
P-C＝3.1Hz)，129.9，128.7，127.6，127.1，126.8，123.1(q，JC-F＝272.9Hz)，122.5(d，J
P-C＝1.9Hz)，121.5.
19F?NMR(376MHz，CDCl
3)δ＝96.3.
C2:(S)-3,3 '-(phenylbenzene anthryl)-phosphoric acid
(S)-3，3’-Biphenanthrylphosphoric?Acid
Make 90% yield from corresponding diphenol.[α]
D 20＝528°(c＝0.10，MeOH)；
1H?NMR(300MHz，DMSO-d
6)：
6.42(d，J＝7.4Hz，4H)，6.85(t，J＝7.6Hz，4H)，7.01(t，J＝7.7Hz，2H)，7.44-7.87(m，12H)，9.87(d，J＝8.5Hz，2H)；
31P?NMR(DMSO-d
6)
3.17。
C3:(S)-3,3 '-[two 2-yls] 2-1,1 '-binaphthol phosphoric acid
(S)-2，6-Bis-(naphthalen-2-yl)-4-oxo-3，5-dioxa-4λ
5-phospha-cyclohepta[2，1-a；3，4-a′]dinaphthalen-4-ol
86% yield; [α]
D 23=322.8 ° of (c=1.02, CHCl
3);
1HNMR (300MHz, DMSO-d6.) δ 7.13 (s, 2H), 7.36-7.26 (m, 2H), 7.42-7.62 (m, 6H), 7.92-8.06 (m, 6H), 8.12 (d, 2H, J=8.4Hz), 8.23 (s, 2H), 8.27-8.36 (m, 2H), 8.51 (s, 2H);
13C NMR (75MHz, DMSO-d6)
122.76,124.90,126.00,126.01,126.27,127.02,127.47,128.28,128.51,128.92,129.05,130.23,130.63,131.93,132.15,132.99,134.37,135.79,147.55,147.68; HRMS calculated value [M+H] (C
40H
26O
4P) m/z 601.1569, measured value m/z 601.1565.
C4:(S)-3,3 '-[two (triphenyls) are silica-based] 2-1,1 '-binaphthol phosphoric acid
(S)-2，6-Bis-(triphenylsilyl)-4-oxo-3，5-dioxa-4λ5-phospha-cyclohepta[2，1a；3，4-a′]dinaphthalen-4-ol
(or its enantiomorph)
90 yields; [α]
D 23=156.0 ° (c=1.02, CHCl3);
1H NMR (300MHz, DMSO-d6.) 7.08 (d, 2H, J=8.1Hz), 7.28-7.47 (m, 22H), 7.52-7.63 (m, 12H), 7.87 (d, 2H, J=7.8Hz), 8.05 (s, 2H);
13C NMR (75MHz, DMSO-d6) .121.19,125.41,125.78,126.17,127.74,128.76,129.51,129.76,133.50,134.01,136.32,141.10,152.10,152.12; HRMS calculated value [M+] (C
56H
41O
4Si
2P) m/z 864.2281, measured value m/z 864.2296..
C5:(S)-3,3 '-(phenylbenzene)-2-1,1 '-8 hydrogen-binaphthol phosphoric acid
(S)-4-Oxo-2，6-diphenyl--3，5-dioxa-415-phospha-cyclohepta[2，1-a；3，4-a′]dinaphthalen-4-ol
91% yield; [α]
D 28=241.5 ° of (c=0.4, CHCl
3); M.p.286-288 ℃;
1H NMR (DMSO-d6,300MHz) δ (ppm) 1.54-1.61 (m, 3H), 1.77 (m, 3H), 2.16-2.24 (m, 1H), 2.610-2.69 (m, 1H), 2.84-2.86 (m, 2H), 7.20 (s, 1H), 7.31-7.44 (m, 3H), 7.612-7.65 (m, 2H);
13C NMR (DMSO-d6,75MHz) δ (ppm) 22.12,27.33,28.47,127.08,127.15,128.06,129.35,130.85,134.35,136.59,137.14,143.16,143.29; IR (KBr): γ 3422,2931,2856,1447,1253,1219,1019,767,697cm
-1HRMS calculated value (C
32H
28O
4P
1+ Na
2)
+M/z 553.1515, measured value m/z 553.1508.
C6:(S)-3,3 '-[two (to nitro) phenyl] 2-1,1 '-binaphthol phosphoric acid
(S)-3，3′-[4-(nitro)phenyl]2-1，1′-binaphthyl?phosphate
Yellow solid,
1HNMR (300MHz, DMSO-d
6) δ 7.18-7.21 (m, 2H), 7.41 (t, J=7.5Hz, 2H), 7.56 (t, J=7.5Hz, 2H), 8.13-8.18 (m, 6H), 8.32-8.35 (m, 6H),
31P NMR (75MHz, DMSO-d
6) δ 2.92;
C7:(S)-3,3 '-(two 1-naphthyls) 2-1,1 '-binaphthol phosphoric acid
(S)-2，6-Bis-(naphthalen-1-yl)-4-oxo-3，5-dioxa-4λ
5-phospha-cyclohepta[2，1-a；3，4-a′]dinaphthalen-4-ol
White solid,
1H NMR (300MHz, DMSO-d
6) δ 7.48-7.66 (m, 16H), 7.99-8.01 (m, 4H), 8.15-8.18 (m, 4H),
31PNMR (75MHz, DMSO-d
6) δ 1.64;
C8:(R)-3,3 '-(two 1-naphthyls) 2-1,1 '-binaphthol phosphoric acid
(R)-2，6-Bis-(naphthalen-1-yl)-4-oxo-3，5-dioxa-4λ
5-phospha-cyclohepta[2，1-a；3，4-a′]dinaphthalen-4-ol
White solid,
1H NMR (300MHz, DMSO-d
6) δ 7.48-7.67 (m, 16H), 7.99-8.02 (m, 4H), 8.15-8.18 (m, 4H),
31PNMR (75MHz, DMSO-d
6) δ 1.65;
C9:((4R, 5R)-2,2-dimethyl-1,3-dioxolane-4,5-two replaces) two (diphenyl methyl)-phosphoric acid
((4R，5R)-2，2-dimethyl-1，3-dioxolane-4，5-diyl)bis(diphenylmethanyl)-phosphate
White solid,
31P NMR (75MHz, DMSO-d
6) δ 3.52; HRMS calculated value (C
31H
29O
6P)
+M/z528.1702, measured value m/z 528.1711.
Embodiment 2: the acid catalyzed Benzazole compounds of chiral phosphorus is to the addition reaction of sulfimide
In an exsiccant reaction tubes, add (chirality) phosphate cpd (0.025mmol) successively, sulfimine compound (0.25mmol), toluene 1mL, stirred 10 minutes under the room temperature, put into-60 ℃ of baths again and stirred 5 minutes, add Benzazole compounds (0.75mmol) ,-60 ℃ of reactions down, reaction finishes, and adds 10%NaHCO
3The aqueous solution (3mL), separatory, organic layer is washed once with 5mL, and saturated aqueous common salt 5mL washes once, the organic layer anhydrous Na
2SO
4Drying, the residue column chromatography for separation gets product after the removal of solvent under reduced pressure.
P1:(R)-N-((3-(1 hydrogen-indoles) base) (phenyl methyl)-4-aminomethyl phenyl sulphonamide
(R)-N-((1H-indol-3-yl)(phenyl)methyl)-4-methylbenzenesulfonamide
Catalyzer is C7 (10mol%) ,-60 ℃; R
f=0.40 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 83% productive rate, 98%ee[Daicel Chiralcel OD-H, Hexanes/IPA=70/30,0.6mlmin
-1, λ=254nm, t (major)=16.92min, t (minor)=32.54min]; [α]
D 20=+15.3 ° (c=0.52, Acetone).
1H NMR (300MHz, CDCl
3) δ 2.34 (s, 3H), 5.24 (d, J=7.2Hz, 1H), 5.82 (d, J=6.9Hz, 1H), 6.61 (d, J=2.4Hz, 1H), 6.97 (t, J=7.8Hz, 1H), 7.06 (d, J=7.8Hz, 2H), 7.11-7.27 (m, 8H), 7.53 (d, J=8.4Hz, 2H), 8.02 (br, 1H);
13C NMR (75MHz, DMSO-d
6) δ 20.8,54.4,111.4,115.7,118.8,118.9,121.2,123.7,125.4,126.4,126.6,127.0,127.8,128.9,136.3,138.8,141.7,141.8.
P2:(R)-N-((3-(1 hydrogen-indoles) base) (phenyl methyl)-phenyl-sulfamide
(R)-N-((1H-indol-3-yl)(phenyl)methyl)benzenesulfonamide
Catalyzer is C7 (5mol%) ,-60 ℃; R
f=0.40 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 88% productive rate, 99%ee.
1H NMR (300MHz, CDCl
3) δ 5.22 (d, J=7.2Hz, 1H), 5.88 (d, J=7.5Hz, 1H), 6.62 (d, J=2.4Hz, 1H), 7.00 (t, J=7.5Hz, 1H), 7.13-7.31 (m, 10H), 7.43 (t, J=7.5Hz, 1H), 7.65 (d, J=7.2Hz, 2H), 8.02 (br, 1H);
13C NMR (75MHz, CDCl
3) δ 55.0,111.3,116.2,119.2,120.0,122.5,123.8,125.3,127.0,127.1,127.4,128.3,128.6,132.2,136.5,140.0,140.4.
P3:(S)-N-((3-(1 hydrogen-indoles) base) (phenyl methyl)-phenyl-sulfamide
(S)-N-((1H-indol-3-yl)(phenyl)methyl)benzenesulfonamide
Catalyzer is C8 (5mol%) ,-60 ℃; R
f=0.40 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 89% productive rate, 99%ee.
1H NMR (300MHz, CDCl
3) δ 5.23 (d, J=7.2Hz, 1H), 5.88 (d, J=7.5Hz, 1H), 6.62 (d, J=2.4Hz, 1H), 7.00 (t, J=7.5Hz, 1H), 7.13-7.32 (m, 10H), 7.43 (t, J=7.5Hz, 1H), 7.65 (d, J=7.2Hz, 2H), 8.02 (br, 1H);
13C NMR (75MHz, CDCl
3) δ 55.0,111.3,116.2,119.2,120.0,122.6,123.8,125.3,127.0,127.1,127.4,128.3,128.6,132.2,136.5,140.0,140.4.
P4:(R)-N-((3-(1 hydrogen-5-methoxyl group indoles) base) (phenyl methyl)-4-aminomethyl phenyl sulphonamide
(R)-N-((5-methoxy-1H-indol-3-yl)(phenyl)methyl)-4-methylbenzenesulfonamide
Catalyzer is C7 (1mol%), room temperature; R
f=0.40 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 87% productive rate, 97%ee.
1H NMR (300MHz, CDCl
3) δ 2.24 (s, 3H), 3.63 (s, 3H), 5.56 (d, J=7.5Hz, 1H), 5.73 (d, J=7.5Hz, 1H), 6.44 (d, J=1.8Hz, 1H), 6.69-6.73 (m, 2H), 6.94 (d, J=8.1Hz, 2H), and 7.03-7.14 (m, 6H), 7.44 (d, J=7.8Hz, 2H), 8.18 (br, 1H);
13C NMR (75MHz, CDCl
3) δ 21.3,54.9,55.6,100.8,112.0,112.4,115.5,124.6,125.8,126.9,127.0,127.1,128.1,129.1,131.5,137.3,140.1,142.8,153.7; MS (EI): m/z (%relativeintensity) 406 (M
+, 4), 91 (100), 171 (55), 235 (51), 155 (48), 107 (23) .HRMS calculated value (M
+) C
23H
22N
2O
3S:406.1351. measured value: 406.1346.
P5:(R)-N-((3-(1 hydrogen-5-methoxyl group indoles) base) (phenyl methyl)-phenyl-sulfamide
(R)-N-((5-methoxy-1H-indol-3-yl)(phenyl)methyl)benzenesulfonamide
(or its enantiomorph)
Catalyzer is C7 (2mol%), 0 ℃; R
f=0.30 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 84% productive rate, 99%ee.
1H NMR (300MHz, CDCl
3) δ 3.71 (s, 3H), 5.44 (d, J=7.2Hz, 1H), 5.84 (d, J=7.5Hz, 1H), 6.52 (d, J=2.7Hz, 1H), 6.79dd, J
1=2.4Hz, J
2=9.0Hz, 1H), 6.85 (d, J=1.8Hz, 1H), 7.12-7.25 (m, 8H), 7.38 (t, J=7.5Hz, 1H), 7.62 (d, J=8.1Hz, 2H), 7.96 (br, 1H);
13C NMR (75MHz, CDCl
3) δ 55.1,55.8,76.6,77.0,77.4,100.9,109.7,112.0,115.8,124.5,125.8,126.9,127.1,127.4,128.3,128.6,131.5,132.1,139.9,154.1; MS (EI): m/z (%relative intensity) 392 (M
+, 2), 235 (100), 77 (52), 165 (37), 220 (37), 93 (18) .HRMS calculated value (M
+) C
22H
20N
2O
3S:392.1201. measured value: 392.1202.
P6:(R)-N-((3-(1 hydrogen-5-skatole) base) (phenyl methyl)-4-aminomethyl phenyl sulphonamide
(R)-4-methyl-N-((5-methyl-1H-indol-3-yl)(phenyl)methyl)benzenesulfonamide
(or its enantiomorph)
Catalyzer is C7 (10mol%) ,-60 ℃; R
f=0.30 (ethyl acetate/petroleum ether=1/3, v/v); Solid, 89% productive rate,＞99%ee.
1H NMR (300MHz, CDCl
3) δ 2.28 (s, 3H), 2.34 (s, 3H), 5.22 (d, J=6.6Hz, 1H), 5.74 (d, J=6.6Hz, 1H), 6.43 (s, 1H), 6.85 (s, 1H), 6.92 (d, J=8.7Hz, 1H), 7.06-7.10 (m, 3H), and 7.16-7.20 (m, 5H), 7.53 (d, J=7.8Hz, 2H), 7.95 (br, 1H);
13C NMR (75MHz, CDCl
3) δ 21.3,21.4,54.7,111.0,115.5,118.4,123.9,124.2,125.5,127.0,127.1,128.2,128.9,129.2,134.7,137.2,140.4,143.0.
P7:(R)-N-((3-(1 hydrogen-5-skatole) base) (phenyl methyl)-phenyl-sulfamide
(R)-N-((5-methyl-1H-indol-3-yl)(phenyl)methyl)benzenesulfonamide
Catalyzer is C7 (10mol%) ,-60 ℃; R
f=0.40 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 83% productive rate, 99%ee.
1HNMR (300MHz, CDCl
3) δ 2.31 (s, 3H), 5.22 (d, J=6.9Hz, 1H), 5.81 (d, J=6.9Hz, 1H), 6.47 (d, J=2.4Hz, 1H), and 6.95-6.97 (m, 2H), 7.12-7.24 (m, 6H), 7.30 (t, J=7.8Hz, 2H), 7.44 (t, J=7.2Hz, 1H), 7.67 (d, J=7.2Hz, 2H), 7.90 (br, 1H);
13CNMR (75MHz, CDCl
3) δ 21.4,54.9,110.9,115.6,118.5,124.1,125.5,127.0,127.1,127.3,128.2,128.6,129.2,132.2,134.7,140.2,140.3; MS (EI): m/z (%relativeintensity) 376 (M
+, 8), 219 (100), 77 (50), 204 (44), 157 (26) .HRMS calculated value (M
+) C
22H
20N
2O
2S:376.1245. measured value: 376.1264.
P8:(R) N-((3-(1 hydrogen-5-bromo indole) base) (phenyl methyl)-4-aminomethyl phenyl sulphonamide
(R)-N-((5-bromo-1H-indol-3-yl)(phenyl)methyl)-4-methylbenzenesulfonamide
Catalyzer is C1 (10mol%), room temperature; R
f=0.30 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 82% productive rate, 98%ee.
1H NMR (300MHz, DMSO-d
6) δ 2.29 (s, 3H), 5.71 (d, J=8.4Hz, 1H), 6.80 (d, J=2.4Hz, 1H), 7.13-7.30 (m, 9H), 7.36 (d, J=1.5Hz, 1H), 7.51 (d, J=8.1Hz, 2H), 8.51 (d, J=8.7Hz, 1H), 11.09 (br, 1H);
13C NMR (75MHz, DMSO-d
6) δ 20.9,53.9,111.3,113.4,115.3,121.1,123.6,1256,126.3,126.7,1269,127.1,127.9,128.9,135.0,138.5,141.5,141.9; MS (EI): m/z (%relative intensity) 454 (M
+, 2), 91 (100), 204 (55), 107 (23) .HRMS (MALDI/DHB): calculated value C
22H
19BrN
2O
2SNa
+(M+Na
+): 477.0253. measured value: 477.0243.
P9:(R)-N-((3-(1 hydrogen-5-bromo indole) base) (phenyl methyl)-phenyl-sulfamide
(R)-N-((5-bromo-1H-indol-3-yl)(phenyl)methyl)benzenesulfonamide
(or its enantiomorph)
Catalyzer is C7 (10mol%) ,-60 ℃; R
f=0.25 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 89% productive rate,＞99%ee.
1H NMR (300MHz, DMSO-d
6) δ 5.76 (d, J=9.0Hz, 1H), 6.81 (d, J=2.1Hz, 1H), 7.14-7.36 (m, 9H), 7.41-7.49 (m, 2H), 7.62 (d, J=7.8Hz, 2H), 8.63 (d, J=9.0Hz, 1H), 11.09 (br, 1H);
13C NMR (75MHz, DMSO-d
6) δ 54.0,111.3,113.4,115.3,121.1,123.6,125.5,126.2,126.7,126.9,127.1,127.9,128.4,131.8,135.0,141.1,141.3; MS (EI): m/z (%relative intensity) 440 (M
+, 4), 77 (100), 204 (93), 157 (50), 93 (37) .HRMS calculated value (M
+) C
21H
17BrN
2O
2S:440.0160. measured value: 440.0175.
P10:(R)-N-((3-(1 hydrogen-6-chloro-indole) base) (phenyl methyl)-4-aminomethyl phenyl sulphonamide
(R)-N-((6-chloro-1H-indol-3-yl)(phenyl)methyl)-4-methylbenzenesulfonamide
Catalyzer is C7 (10mol%) ,-60 ℃; R
f=0.40 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 68% productive rate, 98%ee.
1H NMR (300MHz, DMSO-d
6) δ 2.26 (s, 3H), 5.75 (d, J=8.7Hz, 1H), 6.85 (d, J=2.1Hz, 1H), 6.92 (dd, J
1=1.5Hz, J
2=8.4Hz, 1H), 7.09-7.37 (m, 9H), 7.49 (d, J=8.1Hz, 2H), 8.54 (d, J=9.0Hz, 1H), 11.03 (br, 1H);
13C NMR (75MHz, DMSO-d
6) δ 20.8,54.2,110.9,115.9,118.8,120.2,124.1,124.9,125.9,126.2,126.7,126.9,127.9,128.8,136.7,138.6,141.3,141.8.
P11:(R)-N-((3-(1 hydrogen-6-chloro-indole) base) (phenyl methyl)-phenyl-sulfamide
(R)-N-((6-chloro-1H-indol-3-yl)(phenyl)methyl)benzenesulfonamide
Catalyzer is C7 (10mol%) ,-60 ℃; R
f=0.30 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 87% productive rate,＞99%ee.
1H NMR (300MHz, DMSO-d
6) δ 5.80 (d, J=9.0Hz, 1H), 6.84 (d, J=2.4Hz, 1H), 6.95 (dd, J
1=1.8Hz, J
2=8.4Hz, 1H), 7.13-7.19 (m, 3H), 7.26-7.43 (m, 7H), 7.64 (d, J=7.5Hz, 2H), 8.67 (d, J=9.0Hz, 1H), 11.04 (br, 1H);
13C NMR (75MHz, DMSO-d
6) δ 54.2,111.1,115.9,118.9,120.2,124.2,124.9,126.0,126.2,126.8,126.9,127.9,128.4,131.7,136.7,141.1,141.4; MS (EI): m/z (%relative intensity) 396 (M
+, 4), 204 (100), 239 (81), 77 (56) .HRMS calculated value (M
+) C
21H
17ClN
2O
2S:396.0699. measured value: 396.0710.
P12:(R) N-((3-(1 hydrogen-indoles) base) (p-methylphenyl methyl)-4-aminomethyl phenyl sulphonamide
(R)-N-((1H-indol-3-yl)(p-tolyl)methyl)-4-methylbenzenesulfonamide
Catalyzer is C7 (10mol%) ,-60 ℃; R
f=0.50 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 93% productive rate,＞99%ee.
1H NMR (300MHz, CDCl
3) δ 2.26 (s, 3H), 2.33 (s, 3H), 5.27 (m, 1H), 5.76 (d, J=7.2Hz, 1H), 6.61 (m, 1H), 6.92-6.96 (m, 3H), 7.02-7.10 (m, 4H), 7.12 (d, J=7.2Hz, 1H), 7.22 (d, J=8.1Hz, 2H), 7.50 (dd, J
1=1.8Hz, J
2=8.1Hz, 2H), 8.03 (br, 1H);
13C NMR (75MHz, CDCl
3) δ 20.9,21.4,54.8,111.3,116.2,119.2,119.7,122.2,123.8,125.3,127.1,128.9,129.1,136.5,136.9,137.2,137.3,142.9; MS (EI): m/z (%relative intensity) 390 (M
+, 3), 91 (100), 171 (58), 107 (24) .HRMS calculated value (M
+) C
23H
22N
2O
2S:390.1402. measured value: 390.1398.
P13:(R)-N-((3-(1 hydrogen-indoles) base) (m-nitro ylmethyl)-4-aminomethyl phenyl sulphonamide
(R)-N-((1H-indol-3-yl)(3-nitrophenyl)methyl)-4-methylbenzenesulfonamide
Catalyzer is C1 (20mol%), room temperature; R
f=0.20 (ethyl acetate/petroleum ether=1/2, v/v); Faint yellow solid, 85% productive rate, 89%ee.
1H NMR (300MHz, DMSO-d
6) δ 2.24 (s, 3H), 5.92 (d, J=9.0Hz, 1H), 6.77 (d, J=2.7Hz, 1H), 6.94 (t, J=7.2Hz, 1H), 7.05-7.10 (m, 3H), 7.31-7.49 (m, 5H), 7.71-7.74 (m, 1H), 7.99 (dd, J
1=2.4Hz, J
2=8.4Hz, 1H), 8.07 (s, 1H), 8.68 (d, J=9.0Hz, 1H), 10.99 (br, 1H);
13C NMR (75MHz, DMSO-d
6) δ 20.7,53.7,111.5,114.6,118.7,118.8,121.4,121.5,121.7,124.0,125.2,126.4,128.9,129.3,133.9,136.4,138.3,142.0,143.4,147.4.
P14:(R)-N-((3-(1 hydrogen-indoles) base) (rubigan methyl)-4-aminomethyl phenyl sulphonamide
(R)-N-((4-chlorophenyl)(1H-indol-3-yl)methyl)-4-methylbenzenesulfonamide
(or its enantiomorph)
Catalyzer is C2 (5mol%) ,-30 ℃; R
f=0.40 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 91% productive rate, 94%ee.
1H NMR (300MHz, CDCl
3) δ 2.39 (s, 3H), 5.07 (d, J=5.7Hz, 1H), 5.82 (d, J=6.6Hz, 1H), 6.64 (s, 1H), 7.01 (t, J=7.2Hz, 1H), 7.12-7.21 (m, 8H), 7.31 (d, J=8.4Hz, 1H), 7.56 (d, J=8.1Hz, 2H), 8.02 (br, 1H).
P15:(R)-N-((3-(1 hydrogen-indoles) base) (to the bromophenyl methyl)-4-aminomethyl phenyl sulphonamide
(R)-N-((4-bromophenyl)(1H-indol-3-yl)methyl)-4-methylbenzenesulfonamide
Catalyzer is C3 (10mol%) ,-10 ℃; R
f=0.30 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 71% productive rate, 82%ee.
1H NMR (300MHz, CDCl
3) δ 2.40 (s, 3H), 5.02 (d, J=6.0Hz, 1H), 5.80 (d, J=6.6Hz, 1H), 6.64 (s, 1H), 7.01 (t, J=7.2Hz, 1H), 7.13-7.21 (m, 6H), 7.13-7.21 (m, 3H), 7.56 (d, J=7.8Hz, 2H), 8.01 (br, 1H).
P16:(R)-N-((3-(1 hydrogen-indoles) base) (p-trifluoromethyl phenyl methyl)-4-aminomethyl phenyl sulphonamide
(R)-N-((1H-indol-3-yl)(4-(trifluoromethyl)phenyl)methyl)-4-methylbenzenesulfonamide
Catalyzer is C4 (0.1mol%), 60 ℃; R
f=0.40 (ethyl acetate/petroleum ether=1/2, v/v); Colorlesssolid, 83% productive rate, 85%ee.
1H NMR (300MHz, DMSO-d
6) δ 2.26 (s, 3H), 5.83 (d, J=9.0Hz, 1H), 6.77 (d, J=2.4Hz, 1H), 6.93 (t, J=7.5Hz, 1H), 7.04-7.11 (m, 3H), 7.31-7.39 (m, 2H), 7.45-7.48 (m, 6H), 8.61 (d, J=9.0Hz, 1H), 10.96 (br, 1H);
13CNMR (75MHz, DMSO-d
6) δ 20.8,54.2,110.9,115.9,118.8,120.2,124.1,124.9,125.9,126.2,126.7,126.9,127.9,128.8,136.7,138.6,141.3,141.8.
P17:(R)-N-((3-(1 hydrogen-indoles) base) (m-methoxyphenyl methyl)-4-aminomethyl phenyl sulphonamide
(R)-N-((1H-indol-3-yl)(3-methoxyphenyl)methyl)-4-methylbenzenesulfonamide
Catalyzer is C5 (10mol%) ,-60 ℃; R
f=0.30 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 90% productive rate, 96%ee.
1H NMR (300MHz, CDCl
3) δ 2.31 (s, 3H), 3.62 (s, 3H), 5.44 (d, J=6.9Hz, 1H), 5.78 (d, J=7.2Hz, 1H), 6.58 (s, 1H), 6.67-6.70 (m, 2H), 6.76 (d, J=7.5Hz, 1H), 6.93-7.13 (m, 5H), and 7.20-7.28 (m, 2H), 7.48 (d, J=8.1Hz, 2H), 8.14 (br, 1H);
13CNMR (75MHz, CDCl
3) δ 21.3,54.9,55.0,111.3,112.5,112.9,115.9,119.1,119.6,119.7,122.2,123.8,125.3,127.0,129.1,129.2,136.4,137.3,141.8,142.9,159.4.
P18:(R)-N-((3-(1 hydrogen-indoles) base) (m-methoxyphenyl methyl)-phenyl-sulfamide
(R)-N-((1H-indol-3-yl)(3-methoxyphenyl)methyl)benzenesulfonamide
Catalyzer is C6 (10mol%) ,-60 ℃; R
f=0.30 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 90% productive rate, 97%ee.
1HNMR (300MHz, CDCl
3) δ 3.66 (s, 3H), 5.27 (d, J=7.2Hz, 1H), 5.55 (d, J=6.9Hz, 1H), 6.63 (s, 1H), 6.70-6.74 (m, 2H), 6.80 (d, J=7.8Hz, 1H), 6.98-7.18 (m, 3H), 7.26-7.32 (m, 4H), 7.43 (t, J=7.2Hz, 1H), 7.75 (d, J=7.8Hz, 2H), 8.02 (br, 1H);
13C NMR (75MHz, CDCl
3) δ 55.0,55.1,111.3,112.6,113.1,116.1,119.2,119.6,119.9,122.5,123.8,125.3,127.0,128.6,129.3,132.2,136.5,140.4,141.6,159.5; MS (EI): m/z (%relative intensity) 392 (M
+, 15), 235 (100), 77 (97), 157 (50), 93 (37).
HRMS calculated value (M
+) C
22H
20N
2O
3S:392.1161. measured value: 392.1176.
P19:(S)-N-((3-(1 hydrogen-indoles) base) (m-methoxyphenyl methyl)-phenyl-sulfamide
(S)-N-((1H-indol-3-yl)(3-methoxyphenyl)methyl)benzenesulfonamide
Catalyzer is C8 (10mol%) ,-60 ℃; R
f=0.30 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 92% productive rate, 97%ee.
1H NMR (300MHz, CDCl
3) δ 3.66 (s, 3H), 5.27 (d, J=7.2Hz, 1H), 5.55 (d, J=6.9Hz, 1H), 6.62 (s, 1H), 6.70-6.74 (m, 2H), 6.80 (d, J=7.8Hz, 1H), 6.98-7.18 (m, 3H), 7.26-7.32 (m, 4H), 7.43 (t, J=7.2Hz, 1H), 7.76 (d, J=7.8Hz, 2H), 8.02 (br, 1H);
13C NMR (75MHz, CDCl
3) δ 55.0,55.1,111.2,112.6,113.1,116.1,119.2,119.6,119.9,122.5,123.8,125.3,127.0,128.6,129.3,132.2,136.5,140.4,141.6,159.5; MS (EI): m/z (%relative intensity) 392 (M
+, 16), 235 (100), 77 (97), 157 (50), 93 (37) .HRMS calculated value (M
+) C
22H
20N
2O
3S:392.1161. measured value: 392.1175.
P20:(R)-N-((3-(1 hydrogen-indoles) base) (encircling several ylmethyls)-4-aminomethyl phenyl sulphonamide
(R)-N-(cyclohexyl(1H-indol-3-yl)methyl)benzenesulfonamide
Catalyzer is C7 (10mol%) ,-60 ℃; R
f=0.60 (ethyl acetate/petroleum ether=1/2, v/v); Solid, 56% productive rate, 58%ee.
1H NMR (300MHz, CDCl
3) δ 0.81-1.16 (m, 5H), 1.42-1.46 (m, 1H), 1.57-1.59 (m, 2H), 1.66-1.74 (m, 1H), 1.82-1.85 (m, 1H), 2.00-2.05 (m, 1H), 2.21 (s, 3H), 4.34 (t, J=8.0Hz, 1H), 5.24 (d, J=7.8Hz, 1H), 6.73 (d, J=2.1Hz, 1H), 6.87 (d, J=7.8Hz, 2H), 6.99 (t, J=7.4Hz, 1H), 7.10 (t, J=7.6Hz, 1H), 7.20 (d, J=8.4Hz, 1H), 7.38-7.42 (m, 3H), 7.95 (br, 1H);
13C NMR (75MHz, CDCl
3) δ 21.3,25.9,25.9,26.2,29.8,29.9,42.9,57.1,111.1,114.9,119.1,119.4,121.9,122.5,125.4,126.8,128.6,136.1,137.4,142.3;
P21:(R)-N-((3-(1-methyl-indoles) base) (phenyl methyl)-4-aminomethyl phenyl sulphonamide
(R)-4-methyl-N-((1-methyl-1H-indol-3-yl)(phenyl)methyl)benzenesulfonamide
Catalyzer is C9 (10mol%) ,-60 ℃; Solid, 72% yield, 40%ee;
1H NMR (300MHz, CDCl3) δ 2.24 (s, 3H), 3.47 (s, 3H), 5.26 (d, J=7.2Hz, 1H), 5.74 (d, J=7.2Hz, 1H), 6.39 (s, 1H), 6.89-6.95 (m, 3H), 7.07-7.17 (m, 8H), 7.41 (d, J=8.4Hz, 2H); 13C NMR (75MHz, CDCl3) δ 21.4,32.5, and 54.9,109.2,114.5,119.3,119.4,121.9,125.8,127.1,127.1,127.2,128.2,128.4,129.0,137.2,137.4,140.3,142.8; HRMS: calculated value (M+H+) C23H22N2O2S:390.1395. measured value: 390.1375.
Embodiment 3: the removing and transforming of alkylsulfonyl (application example) in the product
P22:(R)-N-((3-(1 hydrogen-indoles) base) (phenyl methyl)-benzyl carboxamide
(R)-Benzyl(1H-indol-3-yl)(phenyl)methylearbamate
In an exsiccant reaction tubes, add successively P2 (1.10g, 2.5mmol) and dry THF (10mL).Be chilled to-78 ℃ in this solution and add liquefied ammonia (50mL), excess metal sodium (500mg) joins mazarine maintenance 5 minutes in batches then.-78 ℃ add chloride solid (5g) cancellation, and system slowly rises to room temperature, the liquefied ammonia volatilization.Gained residue water (50mL) and methylene dichloride (50mL) layering, organic phase is collected, water dichloromethane extraction (4 * 50mL).Merge organic layer, drying concentrates.The gained white solid is dissolved in THF (30mL), adds entry (15mL).0 ℃ of following high degree of agitation adding yellow soda ash of gained mixture (600mg, 5.66mmol).Outstanding turbid system stirred 5 minutes down for 0 ℃, and (0.60mL 4.2mmol) adds with syringe the benzyl chlorinated carbonates then.Reaction system stirring at room 10 minutes, ethyl acetate dilution (100mL) then.Organic phase is collected, and drying concentrates, column chromatography purification (silica gel petrol ether/ethyl acetate: 4/1) obtain as topic compound (900mg, 99% productive rate).99%ee; M.p.144-145 ℃;
1HNMR (300MHz, CDCl
3) δ 5.13 (two doublets, AB, J=12Hz, 2H), 5.47 (d, J=7.2Hz, 1H), 6.26 (d, J=7.2Hz, 1H), 6.69 (s, 1H), 7.06 (t, J=8Hz, 1H), 7.18 (t, J=8Hz, 1H), and 7.24-7.40 (m, 11H), 7.46 (d, J=8Hz, 1H), 8.11 (br, 1H);
13C NMR (100MHz, CDCl
3) δ 52.3,66.9,111.3,115.7,117.30,119.35,119.9,112.5,123.3,125.7,126.8,127.3,128.1,128.4,136.4,136.6,141.5; IR (neat) v3466,3055,1719,1498,1265,742cm
-1.HR-MS: calculated value (M+Na
+) for C
23H
20N
2O
2, 379.1422; Measured value, 379.1415.
Claims (7)
1. the method for a synthetic 3-methyl amino indole compound, it is characterized in that in the presence of organic solvent and-78 ℃～100 ℃, with sulfimide and indoles is raw material, with the chirality organic phosphoric acid is catalyzer, react and made the 3-methyl amino indole compound in 10 minutes-48 hours, the mol ratio of described sulfimide, benzazolyl compounds, chirality organic phosphoric acid is 1: 1-10: 0.01-1;
The structural formula of described indoles is
The structural formula of described sulfimide is
R wherein
1Be selected from H or C arbitrarily
1-C
16Alkyl; R
2Be H, halogen, C
1-C
16-oxyl, C
1 -C
16Alkyl or amino; R
3Be H; R
4, R
5, R
6Or R
7Be selected from H, halogen, C arbitrarily
1-C
16-oxyl or C
1-C
16Alkyl; R
8Be selected from H or C arbitrarily
1-C
16Alkyl; R
9Be selected from C arbitrarily
1 -C
16Alkyl, the aryl of replacement
R wherein
11, R
12, R
13, R
14, R
15Be selected from H, halogen, C arbitrarily
1-C
16Perfluoroalkyl, nitro, C
1-C
16-oxyl or C
1-C
16Alkyl;
R
10Be selected from the aryl or the C of replacement arbitrarily
1-C
16Alkyl, the substituting group on the described substituted aryl is H, halogen, C
1-C
16-oxyl, C
1-C
16Alkyl or amino.
2. the method for synthetic 3-methyl amino indole compound according to claim 1 is characterized in that described product 3-methyl amino indole compound is optically active, and its structural formula is
Wherein * represents chiral carbon atom, R
1, R
2, R
4, R
5, R
6, R
7, R
8, R
9, R
10According to claim 1.
3. the method for synthetic 3-methyl amino indole compound according to claim 1 and 2, the structural formula that it is characterized in that described organic phosphoric acid catalyst are optically pure following compound or its enantiomorph:
Wherein: R
16, R
17, R
18, R
19, R
20Be selected from H, C arbitrarily
1-C
16Silica-based, the aryl of alkyl, replacement or the aryl of replacement; Substituting group on silica-based, the aryl that replaces of described replacement is H, halogen, CF
3, nitro, C
1-C
16-oxyl, C
1-C
16Alkyl or amino.
4. the method for synthetic 3-methyl amino indole compound according to claim 1 is characterized in that described organic solvent is benzene, tetracol phenixin, sherwood oil, tetrahydrofuran (THF), dimethyl formamide, ether, methylene dichloride, trichloromethane, toluene, dimethylbenzene, hexanaphthene, normal hexane, normal heptane, dioxane or acetonitrile.
5. the method for synthetic 3-methyl amino indole compound according to claim 1, the mol ratio that it is characterized in that described sulfimide, benzazolyl compounds and chirality organic phosphoric acid three is 1: 1-4: 0.05-0.2.
6. the method for synthetic 3-methyl amino indole compound according to claim 1 is characterized in that described temperature of reaction is-60 ℃～25 ℃.
7. the method for synthetic 3-methyl amino indole compound according to claim 1 is characterized in that products therefrom is separated through recrystallization, thin-layer chromatography or column chromatography underpressure distillation.
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| CN103012364B (en) * | 2011-09-28 | 2014-08-06 | 中国科学院化学研究所 | Method for preparing photoactive tetrahydrofuran derivative |
| CN102503881B (en) * | 2011-11-11 | 2013-08-07 | 华东师范大学 | Optically active tryptamine derivative and synthetic method and application thereof |
| CN103012029B (en) * | 2012-12-17 | 2015-04-29 | 中国科学院化学研究所 | Method for synthesizing photoactive pyrrole or photoactive piperidine |
| CN105153011B (en) * | 2015-07-13 | 2018-06-26 | 常州大学 | A kind of synthetic method of 2- sulfimides indoline |
| CN113461589B (en) * | 2021-07-27 | 2022-10-14 | 上海工程技术大学 | Chiral 2, 3-disubstituted indoleamine compound and preparation method thereof |
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| US6500853B1 (en) * | 1998-02-28 | 2002-12-31 | Genetics Institute, Llc | Inhibitors of phospholipase enzymes |
| WO2006033446A1 (en) * | 2004-09-21 | 2006-03-30 | Astellas Pharma Inc. | Aminoalcohol derivatives |
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